Cyanidin-3-O-β-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IκBα phosphorylation in THP-1 cells
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Objective and design
As a common phytochemical, cyanidin 3-O-β-glucoside (C3G) has a role in inhibiting inflammatory mediators; however, its mechanism of action remains unclear. The purpose of this study was to explore the effect of C3G on lipopolysaccharide (LPS)-stimulated TNFα and IL-6 expression in the human monocyte/macrophage cell line THP-1, and to explore the mechanisms involved.
Differentiated THP-1 cells were treated with different concentrations of C3G (0.005, 0.05, 0.5,10 μM) in the absence or presence of 1 ng/mL LPS. mRNA expression levels were detected by real time PCR, and secretion of TNFα and IL-6, phosphorylated IκBα, and nuclear factor-kappa B (NF-κB) P65 were monitored by ELISA or Western blotting analysis. The role of an inhibitor of IκBα phosphorylation, BAY 11-7082, in C3G inhibition of LPS-induced cytokines expression was investigated.
C3G (0.05–0.5 μM) treatment significantly inhibited LPS-stimulated TNFα and IL-6 mRNA expression and secretion of these proteins by THP-1 cells. Phosphorylation of IκBα and NF-κB nuclear translocation could be blocked by 0.5 μM C3G. BAY 11-7082 treatment abolished C3G-induced reduction of TNFα and IL-6.
Our results suggest that C3G exerts its anti-inflammatory effect through inhibiting IκBα phosphorylation, thereby suppressing NF-κB activity in THP-1 cells.
KeywordsCyanidin-3-O-β-glucoside Inflammation IκBα IL-6 TNFα
The authors thank Drs. Dayong Wu and Fu Shang in Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, USA for technical advice. This work was a joint research training program supported by the National Natural Science Foundation of China (Grant No. 30730079), and the U.S. Department of Agriculture (Grant No. 1950-51000-064).
- 11.Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol. 2006;26:3071–84.CrossRefPubMedGoogle Scholar
- 31.Jeffes EW 3rd, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate. J Invest Dermatol. 1995;104:183–8.CrossRefPubMedGoogle Scholar